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Antimicrobial Agents and Chemotherapy, October 2009, p. 4153-4158, Vol. 53, No. 10
0066-4804/09/$08.00+0 doi:10.1128/AAC.00041-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Use of Different Inhibitory Quotients To Predict Early Virological Response to Tipranavir in Antiretroviral-Experienced Human Immunodeficiency Virus-Infected Patients
Judit Morello,1
Carmen De Mendoza,2
Vincent Soriano,2
Lourdes Anta,2
Gema González-Pardo,1
Angélica Corral,2
Francisco Blanco,2
Inmaculada Jiménez-Nácher,1
Juan González-Lahoz,2 and
Sonia Rodríguez-Novoa1*
Pharmacology Unit,1 Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain2
Received 12 January 2009/ Returned for modification 17 June 2009/ Accepted 6 July 2009
Information about the relationship between pharmacological parameters and an early virological response to tipranavir (TPV) is scarce. Human immunodeficiency virus (HIV)-infected patients who had received TPV as part of a salvage regimen were analyzed retrospectively. A virological response was defined as a decline in the HIV RNA level of 
1 log unit or to <50 copies/ml between weeks 4 and 12 of therapy. The virtual inhibitory quotient (vIQ) was calculated as the ratio of the TPV plasma trough concentration (Ctrough)/virtual change in the 50% inhibitory concentration. Three genotypic inhibitory quotients (gIQs) were calculated by using different TPV resistance mutation scores (from the International AIDS Society—USA [IAS-USA], Randomized Evaluation of Strategic Intervention in Multidrug-Resistant Patients with Tipranavir [RESIST], and Agence Nationale de Recherches sur le Sida et les Hépatites Virales [ANRS] trials). The sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and likelihood ratios for a positive result (LHR+) and a negative result (LHR–) [LHR+ = sensitivity/(1 – specificity); LHR– = (1 – sensitivity)/specificity] were calculated. A total of 57 HIV-infected patients were analyzed. A virological response was achieved by 77% of the patients. TPV resistance mutations, TPV Ctrough, vIQs, and gIQs were all significantly associated with a virological response. The vIQ had the best PPV and NPV (97% and 78%, respectively). The values of the LHR+ were 7.8 for vIQ, 3.4 for the RESIST gIQ, 3.3 for the IAS-USA gIQ, 3.1 for the ANRS gIQ, 2.2 for TPV Ctrough, and 1.3 for the IAS-USA and RESIST scores. The values of LHR– were 0 for the RESIST score, 0.07 for vIQ, 0.09 for the IAS-USA score, 0.27 for the RESIST gIQ, 0.32 for the IAS-USA gIQ, 0.37 for the ANRS gIQ, and 0.48 for TPV Ctrough. HIV-infected patients who initiate a salvage regimen based on TPV may benefit from baseline drug resistance testing and TPV plasma concentration determination, as vIQ is the best predictor of a virological response.
* Corresponding author. Mailing address: Service of Pharmacy, Hospital Carlos III, Calle Sinesio Delgado 10, Madrid 28029, Spain. Phone: 34 91 4532694. Fax: 34 91 4532696. E-mail: sonia_r_novoa{at}hotmail.com
Published ahead of print on 13 July 2009.
Antimicrobial Agents and Chemotherapy, October 2009, p. 4153-4158, Vol. 53, No. 10
0066-4804/09/$08.00+0 doi:10.1128/AAC.00041-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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